Approximately 80% of low-grade glioma (LGGs) harbor mutant isocitrate dehydrogenase 1/2 (IDH1/2) driver mutations leading to accumulation of the oncometabolite 2-hydroxyglutarate (2-HG). Thus, inhibition of mutant IDH is considered a potential therapeutic target. Several mutant IDH inhibitors are currently in clinical trials, including AG-881 and BAY-1436032. However, to date, early detection of response remains a challenge. In this study we used high resolution 1H magnetic resonance spectroscopy (1H-MRS) to identify early noninvasive MR (Magnetic Resonance)-detectable metabolic biomarkers of response to mutant IDH inhibition. In vivo 1H-MRS was performed on mice orthotopically-implanted with either genetically engineered (U87IDHmut) or patient-derived (BT257 and SF10417) mutant IDH1 cells. Treatment with either AG-881 or BAY-1436032 induced a significant reduction in 2-HG. Moreover, both inhibitors led to a significant early and sustained increase in glutamate and the sum of glutamate and glutamine (GLX) in all three models. A transient early increase in N-acetylaspartate (NAA) was also observed. Importantly, all models demonstrated enhanced animal survival following both treatments and the metabolic alterations were observed prior to any detectable differences in tumor volume between control and treated tumors. Our study therefore identifies potential translatable early metabolic biomarkers of drug delivery, mutant IDH inhibition and glioma response to treatment with emerging clinically relevant therapies.Seasonality is a critical source of vulnerability across most human activities and natural processes, including the underlying and immediate drivers of acute malnutrition. However, while there is general agreement that acute malnutrition is highly variable within and across years, the evidence base is limited, resulting in an overreliance on assumptions of seasonal peaks. We review the design and analysis of 24 studies exploring the seasonality of nutrition outcomes in Africa's drylands, providing a summary of approaches and their advantages and disadvantages. Over half of the studies rely on two to four time points within the year and/or the inclusion of time as a categorical variable in the analysis. While such approaches simplify interpretation, they do not correspond to the climatic variability characteristic of drylands or the relationship between climatic variability and human activities. To better ground our understanding of the seasonality of acute malnutrition in a robust evidence base, we offer recommendations for study design and analysis, including drawing on participatory methods to identify community perceptions of seasonality, use of longitudinal data and panel analysis with approaches borrowed from the field of infectious diseases, and linking oscillations in nutrition data with climatic data.Botrytis squamosa, Botrytis aclada, and Sclerotium cepivorum are three fungal species of the family Sclerotiniaceae that are pathogenic on onion. Despite their close relatedness, these fungi cause very distinct diseases, respectively called leaf blight, neck rot, and white rot, which pose serious threats to onion cultivation. The infection biology of neck rot and white rot in particular is poorly understood. In this study, we used GFP-expressing transformants of all three fungi to visualize the early phases of infection. B. squamosa entered onion leaves by growing either through stomata or into anticlinal walls of onion epidermal cells. B. aclada, known to cause post-harvest rot and spoilage of onion bulbs, did not penetrate the leaf surface but instead formed superficial colonies which produced new conidia. S. cepivorum entered onion roots via infection cushions and appressorium-like structures. In the non-host tomato, S. cepivorum also produced appressorium-like structures and infection cushions, but upon prolonged contact with the non-host the infection structures died. With this study, we have gained understanding in the infection biology and strategy of each of these onion pathogens. Moreover, by comparing the infection mechanisms we were able to increase insight into how these closely related fungi can cause such different diseases.Computer-aided simulations have long been of great importance in university teaching; however, to date, there is limited use of such simulations in the dental surgical sector. For this purpose, an oral surgery simulator, "Kobra", was implemented in student training and was evaluated for dental education. https://www.selleckchem.com/products/Verteporfin(Visudyne).html Dental students (group 1, third-year and group 2, fourth-year) and dentists of the faculty (control group) were trained to use the simulator. The outcomes for group 1 (apicoectomy of an upper lateral incisor with Kobra), group 2 (removal of an impacted lower wisdom tooth with Kobra) and the control group (both procedures with Kobra) were evaluated. For evaluation purposes, subjective parameters (improvement of practical skills, comparison between conventional training and Kobra simulation, and implementation of simulation-based teaching) and objective parameters (removal of bone, tooth substance and soft tissue measured while performing the Kobra simulation) were assessed using questionnaires with a scale ranging from 1-5. A total of 49 students (third-year n = 29, with 22 women and 7 men; fourth-year n = 20, with 17 women and 3 men) and 10 dentists (women n = 5 and men n = 5) participated. Compared to the Kobra simulation, the conventional training method with plastic models was still favored (the difference was non-significant). Compared to the dentists, the simulation data showed a less precise surgical performance of the students (the difference was not significant). The Kobra simulation may offer an additional method to conventional surgery training using plastic models, with benefits for students and faculty staff.The number of people working from home (WFH) increased radically during the coronavirus (COVID-19) pandemic. The purpose of this study was therefore to investigate people's experiences of WFH during the pandemic and to identify the main factors of advantages and disadvantages of WFH. Data from 29 European countries on the experiences of knowledge workers (N = 5748) WFH during the early stages of lockdown (11 March to 8 May 2020) were collected. A factor analysis showed the overall distribution of people's experiences and how the advantages and disadvantages of WFH during the early weeks of the pandemic can be grouped into six key factors. The results indicated that most people had a more positive rather than negative experience of WFH during lockdown. Three factors represent the main advantages of WFH (i) work-life balance, (ii) improved work efficiency and (iii) greater work control. The main disadvantages were (iv) home office constraints, (v) work uncertainties and (vi) inadequate tools. Comparing gender, number of children at home, age and managers versus employees in relation to these factors provided insights into the differential impact of WFH on people's lives.